1. Plug-and-Play Multicellular Circuits with Time-Dependent Dynamic Responses
- Author
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Javier Macía, David Canadell, Francesc Posas, Eva Gonzalez-Flo, Arturo Urrios, and Eulàlia de Nadal
- Subjects
0301 basic medicine ,Saccharomyces cerevisiae Proteins ,Time Factors ,Monosaccharide Transport Proteins ,Computer science ,Plug and play ,Distributed computing ,Green Fluorescent Proteins ,030106 microbiology ,Glucose Transport Proteins, Facilitative ,Biomedical Engineering ,Cell Communication ,Saccharomyces cerevisiae ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,03 medical and health sciences ,Synthetic biology ,Insulin ,Gene Regulatory Networks ,Sensitivity (control systems) ,Promoter Regions, Genetic ,Biological computation ,Electronic circuit ,Feedback, Physiological ,General Medicine ,Glucagon ,Multicellular organism ,Glucose ,030104 developmental biology ,Proof of concept ,Synthetic Biology ,Microorganisms, Genetically-Modified ,Mating Factor ,Signal Transduction - Abstract
Synthetic biology studies aim to develop cellular devices for biomedical applications. These devices, based on living instead of electronic or electromechanic technology, might provide alternative treatments for a wide range of diseases. However, the feasibility of these devices depends, in many cases, on complex genetic circuits that must fulfill physiological requirements. In this work, we explored the potential of multicellular architectures to act as an alternative to complex circuits for implementation of new devices. As a proof of concept, we developed specific circuits for insulin or glucagon production in response to different glucose levels. Here, we show that fundamental features, such as circuit's affinity or sensitivity, are dependent on the specific configuration of the multicellular consortia, providing a method for tuning these properties without genetic engineering. As an example, we have designed and built circuits with an incoherent feed-forward loop architecture (FFL) that can be easily adjusted to generate single pulse responses. Our results might serve as a blueprint for future development of cellular devices for glycemia regulation in diabetic patients.
- Published
- 2018